Introduction: Cystic fibrosis is the most common autosomal recessive disorder, with a frequency of approximately 1 in 2,500 births. Patients with cystic fibrosis receive lifelong pharmacological treatment and undergo hospitalizations either to manage frequent infections or to receive new therapeutic regimens, resulting in a negative impact on their quality of life. Aim: of the present review was to explore quality of life of patients with cystic fibrosis. Methodology: A literature review was conducted using studies published in the electronic databases PubMed and Scopus. The literature search was performed in English and covered the period from 2013 to 2023. The keywords used were “Cystic Fibrosis, Quality of Life, Determinants.” Results: According to the literature, cystic fibrosis adversely affects the quality of life of patients. Pulmonary exacerbations and low lung expiratory volume reduce patients’ physical functionality, while depression and anxiety similarly affect their psychosocial functioning. The results of the studies indicate that the majority of patients hope to lead a normal life and wish to plan for the future, gaining a sense of control over their condition. The presence of a partner emerged as a significant predictive factor for optimal quality of life, while patients who were parents experienced concerns regarding their health. Regarding the dimensions of quality of life, age was negatively associated with “physical functioning,” “vitality,” and “health perception,” while male gender was positively associated with “physical functioning”. Conclusions: Demographic, clinical, and psychological factors affect the quality of life of patients with cystic fibrosis. Further studies are needed to elucidate the factors affecting quality of life in order to provide high-quality care.